(Press-News.org) In the developing brain, countless nerve connections are made which turn out to be inappropriate and as a result must eventually be removed. The process of establishing a neuronal network does not always prove precise or error free. Dr. Peter Scheiffele's research group at the Biozentrum of the University of Basel have been able to document this phenomenon using advanced microscopy techniques in the developing cerebellum, a brain area required for fine movement control. Dr. Scheiffele's group has discovered that a protein traditionally associated with bone development is responsible for correcting errors while neurons connect to their correct partners in the cerebellum. Their results will be published next week in the online, open access journal PLoS Biology.
The brain is a highly complex set of neuronal networks, in which thousands of different neuron types establish neuronal connections, called synapses, with other neurons. To establish these synapses, neurons send out axons from their cell bodies, which are fiber like extensions that extend into the various regions of the brain. Each neuron must connect with particular partner neurons during brain development, and it is this precise specificity which allows different circuits and different brain regions to serve different functions. The cerebellum, for example, has very precise connectivity that allows the brain to use sensory information (input) and convert it into an exact motor response (output). There are a number of cell types in the cerebellum, two of which are Purkinje cells and granule cells. Mossy fibers are a group of inputs in the cerebellum, which make synaptic connections only with granule cells. In their study, however, Dr. Scheiffele's group have now been able to demonstrate that these mossy fiber inputs often connect with Purkinje neurons during early brain development, in addition to granule cells. These incorrect Purkinje connections are then subsequently eliminated within a week, establishing proper specificity in the cerebellum. They also find that Bone morphogenetic protein 4 (BMP4) helps correct these initial errors. Originally, BMP4 was linked with the specialization of cells during osteogenesis. That this protein is also responsible for the stability and removal of neuronal connections was not previously known.
"If inappropriate connections between neurons are not subsequently eliminated, this can lead to substantial disturbances in the brain. Autism could also be linked to this form of failure to correct errors," explains Scheiffele. The research group at the Biozentrum used a genetic mouse model to make their observations. With the help of a fluorescent protein, the different nerve connections could be stained and made visible by an advanced imaging technique that combines light microscopy with electron microscopy. This allowed multiple types of changes in connectivity to be traced. "These processes can be applied to the development of the human brain and could play an important role in further brain research," added Scheiffele.
The brain undergoes drastic changes during its early life. While the neuronal connections in the brain of a newborn are still relatively unspecific, the selectivity of the synapses steadily increases. The question of what advantage these short-lived, inappropriate connections serve during brain development will become a major focus of Dr. Scheiffele's future research, in addition to their potential implications for neurological disorders such as autism, schizophrenia, and epilepsy.
INFORMATION:
Funding: F.B. is the recipient of a Postdoctoral Fellowship from the Patterson Trust. This work was supported by grants NS 16951 and EY 015290 to C.A.M., and by the Biozentrum of the University of Basel, a DANA Foundation Brain Imaging Award, R01 DA020844, and an award from the Swiss National Science Foundation to P.S..
Competing interests statement: The authors declare that no competing interests exist.
Citation: Kalinovsky A, Boukhtouche F, Blazeski R, Bornmann C, Suzuki N, et al. (2011) Development of Axon-Target Specificity of Ponto-Cerebellar Afferents. PLoS Biol 9(2): e1001013. doi:10.1371/journal.pbio.1001013
END
The health impacts of human rights violations in Chin State, home to the Chin ethnic minority in Burma, are substantial and the indirect health outcomes of human rights violations probably dwarf the mortality from direct killings. These findings from a study by Richard Sollom from Physicians for Human Rights, Cambridge, Massachusetts, USA, and colleagues will be published in this week's PLoS Medicine and should encourage the international community to intensify its efforts to reduce human rights violations in Burma.
The military junta, which seized power in Burma in 1962, ...
In a systematic review of current evidence published in this week's PLoS Medicine, the authors—Jim McCambridge from the London School of Hygiene & Tropical Medicine, London, UK, and colleagues—conclude that there is enough evidence to recommend that reducing drinking during late adolescence is likely to be important for preventing long-term adverse consequences of drinking, as well as protecting against more immediate harms.
Although there is an urgent need for better studies in this area, research to date provides some evidence that high alcohol consumption in late adolescence ...
CHICAGO – Among patients with early-stage breast cancer that had spread to a nearby lymph node and who received treatment that included lumpectomy and radiation therapy, women who just had the sentinel lymph node removed (the first lymph node to which cancer is likely to spread from the primary tumor) did not have worse survival than women who had more extensive axillary lymph node dissection (surgery to remove lymph nodes found in the armpit), according to a study in the February 9 issue of JAMA.
Axillary lymph node dissection (ALND) has been part of breast cancer surgery ...
CHICAGO – Patients who underwent coronary artery bypass graft surgery and had elevated levels of the cardiac enzymes creatine kinase or troponin in the 24 hours following surgery had an associated intermediate and long-term increased risk of death, according to a study in the February 9 issue of JAMA.
"About 400,000 coronary artery bypass grafting (CABG) procedures are performed annually in the United States, giving public health significance to factors that affect the outcome of these procedures," the authors write. Increases in creatine kinase (CK-MB) or troponin levels ...
CHICAGO – In a study that included infants from South Africa, those who were exposed to human immunodeficiency virus (HIV) at birth but did not become infected had lower levels of antibodies to diseases such as pertussis, tetanus and pneumococcus, compared to infants of non-HIV infected mothers, according to a study in the February 9 issue of JAMA.
Infectious diseases account for nearly 6 million deaths worldwide annually in children younger than 5 years. Immunization against vaccine-preventable infections is essential to reducing childhood mortality. "The high prevalence ...
The incidence of major congenital birth abnormalities was slightly higher in the offspring of male cancer survivors compared with children of fathers with no history of cancer, according to a study published online February 8th in the Journal of the National Cancer Institute.
The increasing number of male cancer survivors has given rise to concerns about the health of their offspring. Although previous studies on children conceived naturally have been reassuring about the health of the children, very few studies have looked at results among children conceived through ...
New research from Warwick Medical School published today in the European Heart Journal shows that prolonged sleep deprivation and disrupted sleep patterns can have long-term, serious health implications. Leading academics from the University have linked lack of sleep to strokes, heart attacks and cardiovascular disorders which often result in early death.
Professor Francesco Cappuccio from the University of Warwick Medical School, explained: "If you sleep less than six hours per night and have disturbed sleep you stand a 48 per cent greater chance of developing or dying ...
There will be nearly 1.3 million deaths from cancer in Europe in 2011 according to predictions from a study published in the cancer journal, Annals of Oncology today (Wednesday 9 February) [1].
The estimates, which have been reached after researchers used for the first time in Europe a new mathematical model for predicting cancer mortality, show a fall in overall cancer death rates for both men and women when compared to 2007. But they also highlight some areas of concern, particularly rising rates of lung cancer in women.
Researchers, led by Professor Carlo La Vecchia ...
At a time when the effects of paediatric oncology research have meant that more and more children survive cancer, its funding is too low and dependent on short-term grants to be able to sustain this improvement in the long-term, says a report supported by the EU-funded 7th Framework Programme project Eurocancercoms and published on-line in ecancer today*. The authors also looked at the citation impact of paediatric oncology papers and found that childhood cancer research is once again the poor relation; unlike cancer papers in general, paediatric oncology papers received ...
DETROIT ¬– A Henry Ford Hospital study has found that a pharmacist-directed anticoagulation service improves the way medication is managed for patients with heparin-induced thrombocytopenia (HIT), a common but life-threatening thromboembolic disorder.
Researchers found that patients treated by the anticoagulation service had a favorable response to alternative anticoagulant drugs three times faster and were 32 percent more likely to receive proper dosage than patients who were treated with the same drugs by the patient's primary medical team.
This is the first time ...
